Epigenetics

Epigenetics is an emerging branch of biological research. Its findings will help us understand how information outside DNA can be passed on from cell to cell throughout a person’s life and partially even inherited from generation to generation. Bioinformatician Professor Ivo Grosse explains what epigenetic modifications are all about and how they can be affected by environmental factors.

The epigenomes of twins Mark and Scott Kelly were examined during the NASA Twins Study. (Foto: NASA/Robert Markowitz)

Ever since the famous experiments carried out by Oswald Avery, Colin MacLeod and Maclyn McCarty in 1944 and by Alfred Hershey and Martha Chase in 1952, we have known that genetic information is carried by DNA rather than by proteins. It was long assumed that only genetic information carried by DNA could be passed on to daughter cells in ontogenesis or to children in the course of reproduction. However, we now know that so-called “epigenetic information” can also be passed on from parent cells to daughter cells, and partially even from generation to generation. Epigenetic modifications are considerably more dynamic than mutations in an organism’s DNA, which is modified by environmental factors only weakly.

We now know of various epigenetic mechanisms, the most investigated of which is DNA methylation. This is where, under certain conditions, a methyl group is attached to one of the four DNA bases or disconnected from them. This leads to the emergence of so-called “methylation patterns,” which influence which areas of DNA are accessible to so-called “transcription factors” and how strongly genes can be activated or deactivated.

Another mechanism is histone modification. DNA is bound to proteins, so-called “histones” and their protein complexes. They too carry information that can be passed on from parent cells to daughter cells and partially even from generation to generation. During histone modification, small chemical molecules are attached to certain parts of the proteins or disconnected from them. This molecular-biological process is different from DNA methylation, but it similarly affects the activation and deactivation of genes.

Another important epigenetic mechanism is the concentration of so-called “non-coding RNAs” which similarly affect gene activity and the concentration of messenger RNAs.

The human genome contains approximately 30 million sites that can be methylated or demethylated. This means that a large amount of information can be stored in the methylation pattern of each individual cell. A huge amount of further information is also contained in the patterns of histone modifications and RNA concentrations. Bioinformaticians develop algorithms to analyse all of this information with the long-term goal of deepening our understanding of how these epigenetic patterns change in time in the course of ontogenesis and ageing, in space from cell type to cell type, or by different diseases.

In principle, epigenomes are modified by all environmental factors. These do not only include chemical and physical processes like light and heat radiation, noise, or air pollution, but they also include biological, psychological, and social factors like a person’s diet, lifestyle, or stress as well as diseases, allergies, or poisoning. A person’s diet during childhood and infancy, for example, partially influences whether this person will become overweight or thin in later life. Even a mother’s eating habits during pregnancy can modify her epigenome and that of her child.

Many highly interesting studies have been undertaken in the field of epigenetics. The feeding of bee larvae, for example, influences whether they will become worker bees or queens, as this modifies their epigenomes and leads to the activation and deactivation of different genes. The epigenomes of twins Mark and Scott Kelly are currently being examined as part of the “NASA Twins Study” to better understand the influence of environmental factors on the human epigenome. While one of the twins spent almost one year at the International Space Station (ISS), the other lived on earth, so the twins were exposed to different environmental factors such as different levels of gravity, radiation, or other stress factors.

In the medical field, we are also interested in examining how our epigenomes change during ontogenesis. Many diseases have been found to correlate with epigenetic modifications such as various types of tumour and autoimmune diseases. This is where epigenetics can firstly help to understand how diseases develop on a molecular level. Secondly, it can improve the diagnosis of diseases, for example through the discovery of epigenetic tumour markers. And thirdly, it can lead to new treatment options. Our work has only just begun in this field, however, as it is still unclear in many cases whether an epigenetic change is the cause or the effect of a disease. But there are first promising approaches: Already in 2009, an epigenetic drug was approved in Germany to treat leukaemia through the modification of DNA methylation.

Epigenetics is also important in plants. Some of the current research in Halle aims to find out whether organically grown plants can be distinguished from conventionally grown plants on an epigenetic level. This is particularly interesting because there are more products labelled to be organic on the global market than can actually be produced. No genetic or chemical difference has been found so far, and so we are investigating whether DNA methylation patterns are potentially different in organically grown and conventionally grown soybean and potato plants.

About

Ivo Große (Foto: Maike Glöckner)

Professor Ivo Grosse has been a professor of bioinformatics at the Institute of Computer Science at MLU since 2007. From 2003 to 2007, he led a research group at the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben. Grosse also performs research in the field of epigenetics, for example in the European Training Network “Epidiverse” investigating the adaptation of plants to environmental conditions.